Hormonal drugs — from testosterone replacement therapy to thyroid drugs — change the functioning of entire body systems. To assess exactly how, a starting point is needed: tests taken before the start of the intervention. Clinical guidelines place a lot of emphasis on this basic examination. The editors explain what indicators are included in it, why each one is needed, and why neither safe treatment nor honest risk assessment is possible without them.
Why are tests needed before the start
The first reason is diagnostics. The symptoms people associate with "low testosterone" or "slow metabolism"—fatigue, decreased libido, weight gain, poor recovery—have dozens of possible causes, from lack of sleep and overtraining to anemia, hypothyroidism, depression, or sleep apnea. The Endocrine Society guideline for testosterone therapy emphasizes that the diagnosis of hypogonadism is made only by a combination of symptoms and laboratory-confirmed low levels of the hormone.
The second reason is to identify contraindications. The 2018 guideline identifies conditions requiring avoidance or further evaluation before testosterone therapy, including high hematocrit, prostate or breast cancer, uncontrolled heart failure, severe untreated sleep apnea, desire to have children in the near future. These conditions often have no symptoms and are only detected by tests.
The third reason is safety in dynamics. Hormonal drugs affect blood, lipids, liver, pressure. Without baseline values, it is impossible to know whether the change is a consequence of the treatment or whether it has always been there. That is why the instructions prescribe not only "what to submit before", but also "what to control during".
The fourth reason concerns people who are considering non-medical uses of hormones. The editors do not give any advice on such use and remind that it is associated with proven risks for the heart, liver, psyche and reproductive function. But if a person already consults a doctor, a complete and honest picture of the initial condition is a necessary condition for the doctor to be able to assess the risks and notice complications in time. Good initial tests do not make such an intervention safe.
Hormonal profile: confirm the problem
For men being considered for testosterone therapy, guidelines from the Endocrine Society (2018) and the American Urological Association (2018) recommend measuring total testosterone in the morning, on an empty stomach, at least twice on separate days. The level of the hormone has daily fluctuations and decreases after eating, so one measurement is not enough.
If total testosterone is at the limit of normal or there are conditions that change the level of sex hormone-binding globulin (SHBG), such as obesity, liver disease, hyperthyroidism, age, it is advisable to determine free testosterone by equilibrium dialysis or calculate it from total testosterone, SHBG and albumin.
After confirmation of low testosterone, LH and FSH must be determined. They make it possible to distinguish primary hypogonadism (problem in the testicles, elevated pituitary hormones) from secondary (problem in the pituitary or hypothalamus, LH and FSH are low or "normal"). For secondary hypogonadism, the guidelines recommend additional testing: prolactin, iron saturation of transferrin, assessment of other pituitary functions, and, if indicated, MRI.
| Index | Why is it determined |
|---|---|
| Total testosterone (morning, fasting, twice) | Confirmation of deficiency |
| SHBG, free testosterone | Clarification for borderline values and changes in SHBG |
| LH, FSH | Distinguishing between primary and secondary hypogonadism |
| Prolactin | Exclusion of hyperprolactinemia in secondary hypogonadism |
| TSH, free T4 | Exclusion of thyroid gland pathology imitating symptoms |
| Estradiol | According to clinical indications, for example with gynecomastia |
A baseline hormonal profile is ideally obtained before starting a new treatment that affects the hypothalamic–pituitary–gonadal axis. Tell the clinician about all medicines and supplements so results can be interpreted in context. Do not stop prescribed medicines to obtain a “clean” test unless the prescriber specifically instructs you to do so.
Blood, prostate gland, fertility
Testosterone stimulates the formation of erythrocytes, and an increase in hematocrit is one of the most frequent side effects of therapy. The Endocrine Society guideline classifies a baseline hematocrit of more than 48% (more than 50% for people living high in the mountains) as conditions in which therapy should not be initiated without further evaluation. Therefore, a complete blood count with hematocrit and hemoglobin is included in the mandatory minimum.
Prostate evaluation depends on age and risk factors. The guidelines recommend determining PSA and assessing the risk of prostate cancer in men of the appropriate age groups, and in case of elevated PSA or changes during the examination, consultation with a urologist before starting therapy.
The issue of fertility is separate. Exogenous testosterone suppresses the production of LH and FSH, and therefore spermatogenesis, up to complete azoospermia. A review by Rahnema et al. addresses this very effect in the context of anabolic steroids. Therefore, testosterone therapy is usually not prescribed for men who plan to have children, and a semen analysis before any intervention in the hormonal system is a reasonable step.
It is also useful to have ferritin and iron values for baseline assessment to help interpret future changes in hemoglobin and rule out hemochromatosis, which itself may be the cause of secondary hypogonadism.
Metabolism, liver, kidneys, heart
Hormonal drugs affect lipid profile, insulin sensitivity, liver function and blood pressure. Therefore, the basic examination usually includes:
- lipid panel: total cholesterol, LDL, HDL, triglycerides; once - lipoprotein(a);
- fasting glucose and glycated hemoglobin (HbA1c);
- liver tests: ALT, AST, GGT, bilirubin;
- creatinine with calculation of GFR, urea, electrolytes;
- general analysis of urine;
- blood pressure measurement, according to indications — ECG and echocardiography.
When interpreting liver tests in people who train, it should be remembered that ALT and AST are partly derived from muscles. Therefore, it is useful to simultaneously determine creatine kinase (CK): if it is elevated, "hepatic" enzymes may be of muscle origin. GGT in this sense is more specific for the liver.
Similarly, creatinine in people with large muscle mass or those taking creatine can be higher without kidney damage. In such cases, the doctor may add cystatin C for a more accurate estimate of GFR.
Cardiovascular evaluation is especially important for people with a family history of early heart attacks, hypertension, or dyslipidemia. The Endocrine Society Scientific Statement on Nonmedical Use of Performance Enhancers and the review by Baggish et al describe myocardial damage, accelerated atherosclerosis, and arrhythmias associated with anabolic steroids. The baseline ECG and, if indicated, echocardiography provide a reference point for future comparison.
How to organize an examination
Agree test preparation with the clinician and laboratory: usual sleep, avoidance of unusually heavy exercise beforehand, and morning fasting sampling when required for testosterone assessment. Record all medicines and supplements. A “baseline” test is not a reason to independently discontinue prescribed treatment.
The second rule is one laboratory. Methods for determining testosterone, estradiol, PSA vary between laboratories, and it is difficult to compare the results obtained in different places. If you are planning long-term monitoring, choose a laboratory where you can take tests in the future.
Third, keep the results in one place, with dates and notes about the conditions of collection. This will help the doctor to see the dynamics, and you to understand exactly what has changed.
The fourth is interpretation together with the doctor. An endocrinologist or andrologist will evaluate not only individual numbers, but their combination, taking into account symptoms and accompanying conditions. It is the doctor who determines whether there are indications for therapy and how to control it. Independent conclusions based on online calculators or advice from forums often lead to mistakes.
Testosterone, anabolic agents and many hormone modulators are prohibited under anti-doping rules. Athletes who need treatment should arrange a TUE in advance when required. The rules allow retrospective applications in specified circumstances, including emergency treatment; urgent care must not be delayed to complete paperwork.
Editorial conclusions
The basic examination before hormone therapy performs three functions: it confirms the diagnosis, reveals contraindications, and creates a reference point for further control.
The minimum includes repeated morning measurements of testosterone, LH and FSH, complete blood count with hematocrit, PSA assessment for age, lipids, glucose, liver and kidney parameters, pressure; according to indications — prolactin, TSH, semen analysis, ECG.
Good baseline tests do not make an intervention safe in themselves, but without them, complications cannot be detected in time.
We also advise you to read editorial materials about tests after the course is completed, about lipoprotein(a) as a hidden risk factor, and about CK and liver enzymes in athletes.
References
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744.
- Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423–432.
- Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
- Rahnema CD, Lipshultz LI, Crosnoe LE, et al. Anabolic steroid-induced hypogonadism: diagnosis and treatment. Fertil Steril. 2014;101(5):1271–1279.
- Baggish AL, Weiner RB, Kanayama G, et al. Cardiovascular toxicity of illicit anabolic-androgenic steroid use. Circulation. 2017;135(21):1991–2002.
- World Anti-Doping Agency. The World Anti-Doping Code: International Standard â Prohibited List. Montreal: WADA; оновлÑÑÑÑÑÑ ÑоÑÑÑно.
